ArticleJournal of the American Society of Nephrology : JASN2016
Direct and Indirect Mineralocorticoid Effects Determine Distal Salt Transport.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
95 citing papers in PubMed, 134 citations in OpenAlex.
- Albuminuria is associated with an increased prostasin in urine while aldosterone has no direct effect on urine and kidney tissue abundance of prostasin.Pflugers Archiv : European journal of physiology · 2017Trial
- Comment on "Diet-induced obesity impairs salt-dependent downregulation of NCC activity".Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Diet-induced obesity impairs salt-dependent downregulation of NCC activity.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Chloride at the spotlight-but not alone: towards a multi-ionic diuretic strategy.Clinical kidney journal · 2026Review
- Kidney kallikrein-1 contributes to cleavage of γ-ENaC in vivo.American journal of physiology. Renal physiology · 2026Article
- The Story of Aldosterone Escape.Journal of the American Society of Nephrology : JASN · 2026Review
- Vascular (dys)function in the failing heart.Nature reviews. Cardiology · 2025Review
- Kidney kallikrein-1 contributes to cleavage of gamma-ENaCbioRxiv : the preprint server for biology · 2025Article
- Salt sensitivity of blood pressure: mechanisms and sex-specific differences.Nature reviews. Cardiology · 2025Review
- Successful treatment of severe renal failure caused by malignant hypertension using a combination of renin-angiotensin-aldosterone system inhibitors: a case report.CEN case reports · 2025Article
- Clinical implications of mineralocorticoid receptor overactivation.Clinical kidney journal · 2025Review
- High chloride induces aldosterone resistance in the distal nephron.Acta physiologica (Oxford, England) · 2025Article
- Recent Advances and Perspectives on the Use of Mineralocorticoid Receptor Antagonists for the Treatment of Hypertension and Chronic Kidney Disease: A Review.Biomedicines · 2024Review
- Sodium Chloride Cotransporter in Hypertension.Biomedicines · 2024Review
- Loss of the alpha subunit distal furin cleavage site blunts ENaC activation following NaThe Journal of physiology · 2024Article
- Pathophysiological role of Na-Cl cotransporter in kidneys, blood pressure, and metabolism.Human cell · 2024Review
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- Mineralocorticoid Receptors in Vascular Smooth Muscle: Blood Pressure and Beyond.Hypertension (Dallas, Tex. : 1979) · 2024Review
- Epithelial NaComprehensive Physiology · 2024Review
35 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Excess aldosterone is an important contributor to hypertension and cardiovascular disease. Conversely, low circulating aldosterone causes salt wasting and hypotension. Aldosterone activates mineralocorticoid receptors (MRs) to increase epithelial sodium channel (ENaC) activity. However, aldosterone may also stimulate the thiazide-sensitive Na(+)-Cl(-) cotransporter (NCC). Here, we generated mice in which MRs could be deleted along the nephron to test this hypothesis. These kidney-specific MR-knockout mice exhibited salt wasting, low BP, and hyperkalemia. Notably, we found evidence of deficient apical orientation and cleavage of ENaC, despite the salt wasting. Although these mice also exhibited deficient NCC activity, NCC could be stimulated by restricting dietary potassium, which also returned BP to control levels. Together, these results indicate that MRs regulate ENaC directly, but modulation of NCC is mediated by secondary changes in plasma potassium concentration. Electrolyte balance and BP seem to be determined, therefore, by a delicate interplay between direct and indirect mineralocorticoid actions in the distal nephron.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.